Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies

Area of Science:

• Immunology
• Pathology
• Virology

Background:

• The inflammasome complex regulates cytokine release and cell death, crucial in infections.
• SARS-CoV-2 infection is associated with dysregulated cytokine release, suggesting inflammasome involvement.

Purpose of the Study:

• To investigate inflammasome complex activation in lung tissues of patients deceased from COVID-19.
• To compare SARS-CoV-2 related inflammasome markers with those in influenza A (H1N1) infection and healthy controls.

Main Methods:

• Minimally invasive autopsies and histological analysis (hematoxylin-eosin) of lung samples.
• Immunohistochemical (IHC) staining for inflammasome pathway markers (ACE2, NF-κB, NLRP-3, IL-1β, IL-18, ASC, CASP1, GSDMD, NOX4, TNF-α).
• Statistical analysis of digital IHC data.

Main Results:

• Significantly increased inflammasome activation biomarkers (ACE2, NF-κB, NOX4, ASC) in COVID-19 lung tissue (p < 0.05).
• Markedly elevated pyroptosis and cytokine markers (IL-18, CASP1) in COVID-19, exceeding levels seen in H1N1 infection (p < 0.005 and p < 0.0001, respectively).

Conclusions:

• SARS-CoV-2 pathogenesis is strongly linked to inflammasome complex activation.
• Inflammasome activation and pyroptosis are key features of severe COVID-19, potentially more pronounced than in H1N1 influenza.